Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Kindling is an example of permanent change in brain function that results from repeated elicitation of epileptiform neural activity. The molecular/genetic mechanisms by which kindling is produced and maintained are just beginning to be addressed. Recently two proto-oncogenes, c-fos and c-Ha-ras, have been identified as possible mediators of intracellular signal transduction and may mediate the kindling process. Additionally, c-fos, has been proposed as the gene responsible for turning on molecular events that might underlie the long-term neural changes that occur during kindling. The objective of the present study was to: (i) further investigate the enhancement of c-fos and c-Ha-ras levels following kindled seizures and (ii) investigate the role of c-fos in the plastic changes underlying kindling.;In this study, male hooded rats, were electrically kindled and the resulting c-fos and c-Ha-ras gene expression was quantified using Northern blot analysis. The results indicated that: (i) c-fos was constitutively expressed in forebrain and cerebellum, (ii) basal levels of c-fos were equivalent in naive and in fully kindled rats that has been seizure free for 3 weeks, (iii) an amygdala-pyriform kindled seizure massively and transiently increased c-fos levels, (iv) kindled seizure enhancement of c-fos was observed throughout forebrain and cerebellum, (v) enhancement of AD duration corresponded to enhanced c-fos levels, (vi) enhanced c-fos levels were observed in the amygdala-pyriform contralateral to the kindled site, and the enhancement did not depend on the occurrence of Ad in the contralateral amygdala-pyriform, (vii) electrical stimulations not resulting in AD increased c-fos levels, (viii) c-fos levels were increased by control stimulation, (ix) c-fos induction was partially refractory, (x) PTZ caused c-fos induction independent of a motor convulsion, and (xi) kindled seizures did not alter the expression of c-Ha-ras.;The most parsimonious explanation that accounts for the observations made in this study is that c-fos was expressed simply as a consequence of neural activity and not exclusively due to the specific neural activity (afterdischarge) required for kindling.



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